New ligand bearing preorganized binding side-arms interacting with ammonium cations: Synthesis, conformational studies and crystal structure

Article abstract of DOI:10.1039/b306778e

The synthesis and characterization of the new tetraazamacrocycle 4-(N),10-(N)-bis[2-(3-hydroxy-2-oxo-2H-pyridin-1-yl)acetamido]-1,7-dimethyl-1,4, 7,10-tetraazacyclododecane (L) is reported. L shows two 3-(hydroxy)-1- (carbonylmethylen)-2(1H)-pyridinone moieties as side-arms of a tetra-aza-macrocyclic base. The key coupling of side-arms was studied and the most significant results were obtained by activating the 3-(benzyloxy)-1- (carboxymethyl)-2(1H)-pyridinone as pentafluorophenol ester. The acid-base properties of L and its capability to interact with simple ammonium cations were investigated by potentiometric measurements in aqueous solution (298.1 ± 0.1 K, I = 0.15 mol dm^-3). Protonated species of L can bind NH₄⁺ or primary ammonium cations such as MeNH ₃⁺ discriminating them from secondary or tertiary ammonium cations such as Me₂NH₂⁺ or Me ₃NH⁺ which are not bound in aqueous solution. ¹H and ¹³C NMR spectra showed the existence in solution of two conformers on the NMR time scale due to the rotational restriction of the two N-C=O groups. The activation parameters were determined by dynamic variable-temperature NMR analysis. Molecular dynamics calculations gave results in agreement with the experimental data for both conformation and ammonium-binding studies, underlining that the transformation of the two secondary amines of the macrocyclic base to amide functions, forces the side-arms to remain fixed in position, almost face to face and thus to be preorganized to interact with other species. The crystal structure of the [HL]Cl·8H₂O species shows the high number of preorganized hydrogen bond sites capable, in this case, of interacting directly with five H₂O molecules.